JPH02235808A - Patch for external use - Google Patents

Abstract

PURPOSE:To obtain patch for external use having high affinity for the skin and skin tackiness by itself, containing polyvinyl pyrrolidone, polyvinyl alcohol, sodium carboxymethyl cellulose and sucrose fatty acid ester. CONSTITUTION:(A) Polyvinyl pyrrolidone is blended with (B) polyvinyl alcohol, (C) a sodium carboxymethyl cellulose preferably selected from sodium carboxymethyl cellulose having 0.7-1.4 substitution degree and 900-1,500 [cp] viscosity at 2% and (D) a sucrose fatty acid ester having preferably >=12 HLB value as essential components in the ratio of preferably 0.5-1.0wt.% component A, 1.5-2.0wt.% component B, 3.0-5.0wt.% component C and 1.0-2.0wt.% component D in the whole composition to give a patch for external use having flexibility, viscoelasticity, adhesivity to skin and excellent affinity.

Description

[Detailed description of the invention] [Industrial application field]

The present invention relates to a topical patch that has high affinity for the skin and is itself adhesive to the skin.

[Conventional technology]

Until now, there is a lot of knowledge regarding topical skin preparations aimed at treating diseases locally on the skin. In recent years, there has also been an increase in the development of products aimed at exerting systemic effects, and the usefulness of external preparations for the skin has been highly evaluated. These external skin preparations aimed at exerting local or systemic effects include:
Ointments, liquids, poultices, tapes, etc. are known, but there are problems with appropriate setting of drug dosage, release and permeability of active ingredients, skin compatibility and skin adhesion.
It is hoped that each of these shortcomings will be improved. For example, in the case of ointments, it has been pointed out that it is difficult to determine the exact dosage of the drug depending on the area and thickness to be applied, and that systemic effects cannot be expected. Furthermore, with external skin preparations, there remains the problem that the keratin of the skin acts as a strong barrier, which significantly inhibits the absorption of water-soluble drugs in particular, and research is being conducted into transdermal absorption-promoting agents. However, these accelerators are problematic in terms of skin irritation. On the other hand, in recent years, some drugs (e.g. angina treatment drugs) have been developed based on the idea of the drug delivery system.
Therapeutic System (transdermal absorption treatment system) has been developed, but it has only been put into practical use for a small number of specific drugs, and for drugs in general, only a sufficient amount to exert their useful medicinal effects has been put into practical use. At present, the technology for transdermal absorption has not yet been established.

[Problem B that the invention attempts to solve]

An object of the present invention is to provide a dosage form for external use on the skin that has high affinity for the skin, excellent percutaneous absorption, and is suitable for designing drug dosage.

[Means and effects for solving the problem] The present inventors conducted various studies with the aim of developing a topical preparation that solved the problems in the prior art, and obtained Ayuka polyvinylpyrrolidone, polyvinyl alcohol, carboxymethylcellulose sodium ( (hereinafter abbreviated as CMC-Na) and C.
It was discovered that by incorporating ai fatty acid ester, it is possible to obtain a topical patch that has a high affinity for the skin and is itself skin-adhesive, and by forming this into a thin film, it is possible to administer an appropriate amount of drug through the skin. We have completed the present invention by discovering that a topical patch suitable for absorption into the skin can be obtained. The polyvinyl pyrrolidone used in the present invention preferably has an average molecular weight of about 1.2 million, but even polyvinyl pyrrolidone with a lower molecular weight than this can be used by appropriately adjusting the amount added. Further, the polyvinyl alcohol used in the present invention has an average degree of polymerization of 300 to 700 and a viscosity of 4%.
5-5.5ccF. ] is preferable, but it is not limited to this range, and by adding xi, it is possible to use a higher viscosity one. In addition, the fatty acids of the sucrose fatty acid ester used in the present invention are:
Higher fatty acids such as stearic acid and normitic acid are used. Furthermore, as a result of studying methods to increase the affinity for the skin as well as the stability and shape retention of the formulation, we found that the degree of ether substitution was 0.7-1. 4.2% viscosity is 900-1500
[cP. ], and HLB value is 1.
We discovered that products containing two or more sucrose fatty acid esters are effective. Another effective method for increasing the skin adhesion of the formulation itself is to use polyvinyl pyrrolidone in an amount of 0.5 to 1.0% by weight in the total composition and polyvinyl alcohol in an amount of <1.5 to 2.0% by weight.
0% by weight. CMC-Na is also 3,0 to 5.0% by weight
, 1.0 to 2.0% by weight of sucrose fat rib brewing ester
It was discovered that it can be contained. In addition to the above-mentioned ingredients, the external patch according to the present invention contains (1) gelatin as a base component. solubilized collagen,
water-soluble proteins such as casein and soybean protein; (2) polyhydric alcohols such as glycerin and propylene glycol; (3) multi-ffiQ proteins such as starch and dextrin. (
4) Choose 1 from each item for oily substances such as white petrolatum and squalane! ! Or, in addition to combining multiple types, CMC-N
Celluloses other than a (Melf hydroxyethyl cellulose, hydroxypropyl cellulose, etc.) can be added as appropriate. Furthermore, in addition to the above ingredients, an appropriate amount of water is added in order to maintain the formulation properties such as softness and drug absorption of the topical patch. In this case, the blending amount is usually 30 to 70% by weight, more preferably 40% by weight based on the total composition.
~65% by weight. Also. In order to more effectively express the characteristics of the topical patch, substances other than the above ingredients may be added. As such additives, known additives such as absorption aids, preservatives, pH adjusters, and coloring agents can be used. In addition, in the present invention, there is no need to use astringents such as aluminum silicate, zinc oxide, and kaolin, which are conventionally used in gelatin poultices and the like. The shape of the external patch composed of the above ingredients in the dosage form may be any size and shape that can be easily applied to the skin surface, and may be the same shape as those commonly used as poultices or It is preferable that the material be in the form of a thin film, etc., and have an appropriate thickness and area. For example, the appropriate thickness is usually about 0.3 to 2.0 mm, and the appropriate area is usually about 0.2 to 160 cm2. For use, storage, and handling of the above-mentioned topical patch, if one or both sides of the patch are covered with an appropriate packaging film, the packaging film can be removed at the time of use and the fA released drug surface can be applied to the skin. It is often convenient to have something that just needs to be adhesive. The thickness of such packaging film is 0.02~
0.8mmfi degree synthetic resin Il! (For example, a polyethylene film, a polypropylene film, an elastomer film, a putadiene polymer B), a cellophane film, etc., which are stretchable are preferred, but woven or non-woven fabrics may also be used. In addition. If a topical patch contains volatile ingredients or there is a risk of contamination during storage, it is recommended to store it in an airtight container such as an aluminum pack or a moisture-proof paper bag. The external patch of the present invention is generally soft and has flexibility and viscoelasticity, so it has good adhesion to the skin and feels good when used. Furthermore, cases where the softness of the preparation is increased by moistening the skin-adhesive surface with water during application are also included in the concept of softness in the present invention. The external patch having the above structure is used for medical purposes and is applied to the skin of various parts of the body depending on the treatment purpose and target. For example, in the case of local application, it is applied directly to or near the diseased area, and in the case of systemic application, it is applied to areas with a high percutaneous absorption rate (
For example, it is best to apply it to areas where dead skin cells have not developed) or areas where there is little discomfort. It is also possible to use it for cosmetic purposes by incorporating known cosmetic ingredients. The method for producing the topical patch of the present invention is shown below, but other methods can be used as long as they do not impede the purpose of the present invention. ■Dissolve water-soluble proteins in water. (Dissolution under heating ■Mixture of drug, polyhydric alcohol, oily substance, polysaccharide and water (
At this time, add the additives mentioned above as necessary. ). ■Sucrose fat ugly ester. CMC-Na is sequentially dispersed in polyhydric alcohol at 60°C. ■Sequentially dissolve polyvinylpyrrolidone and polyvinyl alcohol in water at 50°C. Add ■, ■, and ■ to ■■ in sequence at 50'C while stirring vigorously, and continue stirring until the entire preparation has uniform properties. Immediately spread the mixture thinly on a flat plate such as a glass plate, and cover the surface with a film such as polyethylene. Cut ■■ into appropriate size.

【Example】

The present invention will be explained in detail below using examples. 1 Steal 1'' ■ 12g of gelatin was moistened with 25g of purified ice, heated to 50°C, and dissolved. ■Dissolve 2 g of starch in 25 g of special water heated to 50°C, and add 2 ml of methyl salicylate and 0.4 g of camphor. ■ 40g of glycerin contains sucrose fat with HLB value of 15
ester 2.0g and degree of etherification 0.78, 2% viscosity 900-1500 [cP. ] cr) CMC-Na
6. Disperse and dissolve Og while heating to 60°C. ■1 polyvinylpyrrolidone K-90 in 50g of purified water
．． 0g, polyvinyl alcohol (Kuraray Poval 20
Dissolve 3.0 g of 5) in sequence at 50°C. Mix ■■ with ■～■ sequentially at 50℃, and continue stirring until all mixtures are evenly mixed. ■(0 to 20cm x 20cm cotton flannel with thickness 0.8~1
．． 0 mm, immediately cover with polyethylene film, place in a laminated bag, seal, and store at 25°C. Similarly, place ■ on a Petri dish with a diameter of 15 cm to a thickness of 0.8 to 1.
．． Spread it to a thickness of 0 mm, close the lid, and store it in a laminated bag or polyvinyl bag at 25°C to prevent moisture from evaporating. W≧” A formulation was prepared in the same manner as in Production Example 1 according to the formulation in Table 1. However, ingredients not included in the recipe in Production Example 1 shall be dissolved in the purified water in Step 2. Y l ~ 4 A formulation was prepared in the same manner as in Production Example 1 according to the formulations in Table 2. However, gum arabic should be dissolved in the water prepared in Step 2, and polysorbate 80 should be dispersed in the glycerin in Step 2. (Test items) The following items were tested using external patches manufactured by vR in Production Examples 1 to 3 and Comparative Production Examples 1 to 4. After storing the preparation applied to adhesive cotton flannel for a day and night, cut it into 4cm and 4cm pieces, peel off the polyethylene film of each piece, and cut it into 5cm pieces with a diameter of 5cm.
A stainless steel weight of 500 g) is brought into close contact with the plaster of the preparation, the load is allowed to stand for 20 seconds, and the force at which the plaster comes off is measured at a rising speed of 3 cm per minute. Certain equipment, PICMA TACK TESTER manufactured by Toyo Seiki) The results are shown in Table 3. , Sensory test example 1 regarding feeling of use such as adhesion and tackiness
3 and Comparative Production Examples 1 to 4 by removing the ingredients from the formulations and applying the external patches to cotton flannel as samples. Based on Scheffe's method described in ), each test was conducted twice on 10 adults. The specific method is to apply the above sample to the left and right upper arms, remove it after 2 hours, and check how it feels on each of the left and right arms.
Judgments were made based on the following criteria. The results are shown in Table 3. Very good (+3), definitely good (+2), somewhat good (+1), no difference (O). Somewhat bad (-1).
Definitely bad (-2), very bad (-3). 3. Drug dissolution properties The plasters prepared in Production Examples 1 to 3 and Comparative Production Examples 1 to 4 were spread on a Petri dish to form a thin film with a diameter of 4.3 cm.
Cut out a circular shape and apply it to the suppository release test method (Kyoto Pharmaceutical University).
Based on the method (Professor Shozo Muranishi, Pharmacology VOJ2.39, No. 1), the amount of drug elution from the plaster was investigated over time. The results of this test are shown in Table 4. (Test Results) Table 3: Adhesive Strength and Feeling of Use of Preparation As is clear from Table 3, the topical patch of the present invention was evaluated to be better than the comparative example in terms of overall feeling of use, including tackiness and adhesion. Ru. In general, as shown in Table 4, the external patch of the present invention has a sustained drug release effect, and the dissolution rate is considered to be almost constant.

【Effect of the invention】

The present invention contributes to the maintenance, promotion, and recovery of human health and the development of the pharmaceutical industry by providing a topical patch that has flexibility, viscoelasticity, and good adhesion and affinity to the skin. Can contribute. Patent applicant Daiichi Kogyo Seiyaku Co., Ltd.

Claims (1)

[Scope of Claims] 1. An external patch characterized by containing polyvinylpyrrolidone, polyvinyl alcohol, sodium carboxymethyl cellulose, and sucrose fatty acid ester. 2. Sodium carboxymethyl cellulose has a degree of ether substitution of 0.7 to 1.4, a 2% viscosity of 900 to 1500 [c
P. ] The external patch according to claim 1, which is selected from those having the following. 3. The external patch according to claim 1 or 2, wherein the sucrose fatty acid ester has an HLB value of 12 or more. 4. In the whole composition, polyvinylpyrrolidone is 0.5 to 1.
0% by weight, polyvinyl alcohol 1.5-2.0% by weight, sodium carboxymethyl cellulose 3.0-2.0% by weight
The external patch according to claim 1 or 3, which contains 1.0 to 2.0% by weight of 5.0% by weight sucrose fatty acid ester.